Some interrelationships between glucose levels thromboxane production and prostacyclin production in normal and diabetic mice.

We investigated the relationship between glucose levels and platelet thromboxane production or aortic prostacyclin production, using radioimmunoassay (RIA) to measure thromboxane B2 and 6-keto-PGF1 alpha. We found a direct relationship (p less than .05) between plasma glucose levels and thromboxane A2 production by arachidonate stimulated platelets in platelet rich plasma of normal mice. However, when mice were deprived of food overnight, the glucose level fell but the TxB2 production rose significantly. Moreover, mice with streptozotocin diabetes had significantly elevated glucose levels, but normal TxB2 production, which also rose significantly after fasting. Thus in our laboratory both fasting and diabetes nullify or reverse the direct relationship between glucose levels and TxB2 production seen in normal fed mice. This makes it difficult to ascribe the correlation between glucose and TxB2 levels in normal fed animals to cause and effect. RIA revealed an inverse correlation between glucose levels and 6-keto-PGF1 alpha production which was highly significant in aortas taken from fasted mice and stimulated for 10 minutes with 0.1 mM arachidonate. This inverse correlation was present with either normal or diabetic aortas. Moreover, fasting increased the production of 6-keto-PGF1 alpha. However there was a significant elevation of 6-keto production by aortas of mice with diabetes of 5-6 weeks duration, compared to aortas of normal mice. Therefore either diabetes in these mice reversed a normal inhibitory effect of glucose on 6-keto production, or else the inverse correlation between glucose levels and 6-keto production does not represent a cause and effect relationship between the two variables.